A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for adhering spot), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adhesions randomly arranged on the lateral sides of plasma membranes. Desmosomes are one of the stronger cell-to-cell adhesion types and are found in tissue that experience intense mechanical stress, such as cardiac muscle tissue, bladder tissue, gastrointestinal mucosa, and epithelia.
Structure
Desmosomes are composed of desmosome-intermediate filament complexes (DIFCs), a network of cadherin proteins, linker proteins and intermediate filaments. The DIFCs can be broken into three regions: the extracellular core region ("desmoglea"), the outer dense plaque (ODP), and the inner dense plaque (IDP). They bind to each other via heterophilic interactions in the extracellular space near their N-termini, in contrast with the homophilic binding characteristic of other cadherins. Desmoglein and desmocollin have a single pass transmembrane region plus an intracellular anchor to secure its position in the cell membrane. Desmogleins and the desmocollin isoform "Dsc-a" contain an intracellular cadherin domain, which binds to plakoglobin. as it operates as the mediator between the cadherin proteins in the plasma membrane and the keratin filaments. Desmoplakin has two isoforms that differ in the length of their middle rod domain. All desmoplakins have an N-terminal head, a C-tail consisting of three plakin repeats, and a glycine-serine-arginine rich domain (GSR) at the C-end.
Clinical significance
Arrhythmogenic cardiomyopathy
Mutations within the desmosome are the main cause of arrhythmogenic cardiomyopathy (ACM), a life-threatening disease caused by mutations usually in desmoglein 2, but sometimes in desmocollin 2. It often afflicts individuals between 20 and 50 years, and has been publicly known as a cause of death in young athletes, although the majority of sudden deaths do not occur in close connection to physical activity. The current incidence within the population is accepted as 1/10,000; however, it is thought that 1/200 may have a mutation that may predispose to ACM. Symptoms of ACM include fainting, shortness of breath, and heart palpitations and the condition is treated by implanting a small defibrillator device.
Blisters
Blistering diseases such as pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune diseases in which auto-antibodies target desmogleins. PV is caused by circulating autoantibodies (IgG) that target Dsg3 (Desmoglein 3) and sometimes Dsg1. PV is manifested by suprabasal acantholysis, or blisters in the mucous membrane and blisters in the epidermis. PF patients have autoantibodies that target Dsg1 with superficial blisters on the epidermis with no mucous membrane issues. Both diseases result in a loss of keratinocyte adhesion. Pemphigus can also be caused by a bacterial infection: bullous impetigo is an infection caused by a staphylococcus bacterium that releases a toxin that cleaves the Dsg1 extracellular domain.
Similar symptoms occur with Hailey–Hailey disease, though the cause is not autoimmune but genetic. A haploinsufficiency of the ATP2C1 gene located on chromosome 3, which encodes the protein hSPCA1, causes malformation of the desmosomes. Desmoglein 1 haploinsufficiency leads to striate palmoplantar keratoderma, a disease which causes extreme thickening of the epidermis. Loss of desmoglein 4 leads to defective hair-follicle differentiation.